A Phase I Study of JS108 in Patients With Advanced Solid Tumors

A Phase I, Open-label, First-in-human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of Recombinant Humanized Anti-Trop2 mAb-Tub196 Conjugate in Patients With Advanced Solid Tumors.

This is a phase I, open-label, first-in-human clinical study designed to evaluate the safety, tolerability, PK profile and efficacy of JS108 for patients with advanced solid tumors. This study is divided into 3 periods: dose escalation period, dose expansion period, and clinical expansion period.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: JS108 (recombinant humanized anti-Trop2 mAb-Tub196 conjugate for injection)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China, 200433
      • Shanghai Pulmonary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

1. Volunteer to sign an informed consent form.
2. Age of 18-75 years (inclusive), male or female;
3. Expected survival ≥3 months;
4. Histological or cytologically confirmed locally advanced or metastatic solid tumors which progressed on standard of care or with no standard of care available;
5. Toxicity of previous antitumor therapy has recovered to ≤ grade 1 as defined by the NCI-CTCAE v5.0, except alopecia;
6. Subjects dose expansion period and clinical expansion period must have at least one measurable lesion in accordance with RECIST v 1.1;
7. Eastern Cooperative Oncology Group (ECOG) Performance Status score: 0 or 1;
8. Subjects must be able to provide fresh or archived tumor tissue obtained within 1 year prior to inclusion in the study；
9. The organ function level must meet the protocol requirements；
10. Serum pregnancy test confirmed as negative for women of childbearing potential within 7

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dose Escalation

Drug: JS108 (recombinant humanized anti-Trop2 mAb-Tub196 conjugate for injection); Dose escalation period: JS108 is administered intravenously every three weeks (Q3W) at the dose corresponding to the enrolled dose cohort. Dose expansion period: JS108 is administered intravenously Q3W at the corresponding dose. Clinical expansion period: JS108 is administered intravenously Q3W at the recommended dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD)	Number of participants that experienced dose limiting toxicities(DLTs) at given dose level.	A minimum of 21 days after first infusion of study drug
Number of participants with adverse events (AEs)	The adverse events will be evaluated in accordance with CTCAE v5.0. The investigator shall assess the relationship between the events and investigational product.	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed serum or plasma concentration (Cmax)	One of the pharmacokinetics parameters for JS108	Through study completion, an average of 1 year
Maximum serum drug time（Tmax）	One of the pharmacokinetics parameters for JS108	Through study completion, an average of 1 year
Area under the serum or plasma concentration time curve from 0 to infinity (AUC0-inf)	One of the pharmacokinetics parameters for JS108	Through study completion, an average of 1 year
Volume of distribution at steady state (Vss)	One of the pharmacokinetics parameters for JS108	Through study completion, an average of 1 year
Terminal phase elimination half life (t½)	One of the pharmacokinetics parameters for JS108	Through study completion, an average of 1 year
Clearance (CL)	One of the pharmacokinetics parameters for JS108	Through study completion, an average of 1 year
Anti-drug antibodies (ADA)	To evaluate the immunogenicity of JS108 in patients with advanced solid tumors	Through study completion, an average of 1 year
Objective Response Rate (ORR)	As determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, which will be complete response (CR) + partial response (PR)	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year
Duration of response (DOR)	DOR is defined as the time from the date of the first documentation of response (confirmed CR or confirmed PR) to the date of the first documentation of PD or death due to any cause, whichever occurs first.	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year
Progression Free Survival (PFS)	PFS is defined as the time from the date of randomization to the earlier of the dates of the first documentation of progressive disease or death due to any cause.	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year
Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause.	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year
Levels of Trop2 (trophoblast antigen 2) expression in tumor tissue	To investigate any potential correlations of Trop2 levels with responses and toxicity	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2020
• Primary Completion (Actual): June 14, 2023
• Study Completion (Actual): June 14, 2023

Study Registration Dates

• First Submitted: October 12, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 23, 2020

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: JS108-001-I

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No